Abstract:

Purpose: Phosphorylation-related SNP (phosSNP) is a non-synonymous
SNP that might influence protein phosphorylation status. The aim of this study was to
assess the effect of phosSNPs on blood pressure (BP), coronary artery disease (CAD)
and ischemic stroke (IS).

Methods: We examined the association of phosSNPs with BP, CAD and IS in shared
data from genome-wide association studies (GWAS) and tested if the disease loci were
enriched with phosSNPs. Furthermore, we performed quantitative trait locus analysis to
find out if the identified phosSNPs have impacts on gene expression, protein and
metabolite levels.

Results: We found numerous phosSNPs for systolic BP (count=148), diastolic BP
(count=206), CAD (count=20) and IS (count=4). The most significant phosSNPs for
SBP, DBP, CAD and IS were rs1801131 in MTHFR, rs3184504 in SH2B3, rs35212307
in WDR12 and rs3184504 in SH2B3, respectively. Our analyses revealed that the
associated SNPs identified by the original GWAS were significantly enriched with
phosSNPs and many well-known genes predisposing to cardiovascular diseases contain
significant phosSNPs. We found that BP, CAD and IS shared for phosSNPs in loci that
contain functional genes involve in cardiovascular diseases, e.g., rs11556924
(ZC3HC1), rs1971819 (ICA1L), rs3184504 (SH2B3), rs3739998 (JCAD), rs903160
(SMG6). Four phosSNPs in ADAMTS7 were significantly associated with CAD, including
the known functional SNP rs3825807. Moreover, the identified phosSNPs seemed to
have the potential to affect transcription regulation and serum levels of numerous
cardiovascular diseases-related proteins and metabolites.

Conclusion: The findings suggested that phosSNPs may play important roles in BP
regulation and the pathological mechanisms of CAD and IS.

Abstract:Purpose: Phosphorylation-related SNP (phosSNP) is a non-synonymous
SNP that might influence protein phosphorylation status. The aim of this study was to
assess the effect of phosSNPs on blood pressure (BP), coronary artery disease (CAD)
and ischemic stroke (IS).

Methods: We examined the association of phosSNPs with BP, CAD and IS in shared
data from genome-wide association studies (GWAS) and tested if the disease loci were
enriched with phosSNPs. Furthermore, we performed quantitative trait locus analysis to
find out if the identified phosSNPs have impacts on gene expression, protein and
metabolite levels.

Results: We found numerous phosSNPs for systolic BP (count=148), diastolic BP
(count=206), CAD (count=20) and IS (count=4). The most significant phosSNPs for
SBP, DBP, CAD and IS were rs1801131 in MTHFR, rs3184504 in SH2B3, rs35212307
in WDR12 and rs3184504 in SH2B3, respectively. Our analyses revealed that the
associated SNPs identified by the original GWAS were significantly enriched with
phosSNPs and many well-known genes predisposing to cardiovascular diseases contain
significant phosSNPs. We found that BP, CAD and IS shared for phosSNPs in loci that
contain functional genes involve in cardiovascular diseases, e.g., rs11556924
(ZC3HC1), rs1971819 (ICA1L), rs3184504 (SH2B3), rs3739998 (JCAD), rs903160
(SMG6). Four phosSNPs in ADAMTS7 were significantly associated with CAD, including
the known functional SNP rs3825807. Moreover, the identified phosSNPs seemed to
have the potential to affect transcription regulation and serum levels of numerous
cardiovascular diseases-related proteins and metabolites.

Conclusion: The findings suggested that phosSNPs may play important roles in BP
regulation and the pathological mechanisms of CAD and IS.